AB0317 PLASMA NETS LEVELS IN ESTABLISHED RHEUMATOID ARTHRITIS PATIENTS RECEIVING BIOLOGICAL OR JAK INHIBITOR THERAPY AND ASSOCIATION WITH DISEASE ACTIVITY
Authors: B. Frade-Sosa, A. Ponce Fernandez, E. Ruiz-Ortiz, O. Viñas, J. Yagüe, J. M. Auge, A. Azuaga, J. C. Sarmiento-Monroy, R. Morlà, V. Ruiz, J. Ramírez, P. Corzo Garcia, S. M. Farietta Varela, N. Sapena, J. D. D. Cañete, J. A. Gómez-Puerta, R. Sanmartí
Journal: Annals of the Rheumatic Diseases (2023)

<h3>Background</h3> Neutrophil extracellular traps (NETs) may play a pathogenic role in rheumatoid arthritis (RA)<sup>[1]</sup>. Elevated circulating NETs have been found in RA plasma, but their relationship with synovial inflammation and antirheumatic therapy including biologics and JAK inhibitors (JAKi) is unclear. <h3>Objectives</h3> To evaluate whether plasma levels of NETs remnants in patients with established RA are associated with disease activity or type of antirheumatic therapy (biologics or JAKi). <h3>Methods</h3> Observational cross-sectional study. RA patients (ACR/EULAR 2010) receiving treatment with IL6 inhibitors (IL6i), JAKi, or TNF inhibitors (antiTNF) were consecutively included regardless of disease activity and previous therapy. Controls were RA patients with high disease activity (≥ 4 swollen joints), regardless of treatment, as was a second control group of healthy blood donors. Clinical disease activity indexes (DAS28, SDAI, CDAI) and laboratory parameters of inflammation, including high-sensitive CRP (hsCRP) and calprotectin were evaluated. Plasma levels of elastase-DNA (EN-DNA) and histone-DNA complex (H<sub>3</sub>-DNA) (NETs remnants) were examined by ELISA. We analysed NETs remnant levels and clinical variables using Spearman's correlation test. <h3>Results</h3> 111 patients (90.1% female, 85.6% seropositive (RF and/or ACPA), mean age 56.45 years and mean RA duration 15.9 years) were included: 83 received biologics (53 IL6i and 30 antiTNF) and 28 JAKi (19 baricitinib and 9 tofacitinib). Mean DAS28 and CDAI were 3.00 and 10.5, respectively. Controls were 18 active RA patients (mean DAS28 5.72 and CDAI of 34.9), 11 without biological or JAKi treatment [Table 1]. 30 healthy blood donors were also analysed. NETs levels of patients under biologic or JAKi therapy showed no significant differences with healthy controls. No significant differences were observed in NETs values according to the type of therapy. In the control group of patients with high disease activity, plasma NETs were higher than in the main group (treated with JAKi or biologics), but only with statistically significant in H3-DNA levels (EN-DNA 2.96 (sd 5.42) vs 1.25 (sd 1.03) p=0.03; H3-DNA 2.67 (sd 4.52) vs 1.36 (sd 1.15) p &gt;0.05). The two NETs were strongly correlated (ρ=0.97; p&lt;0.001). A weak correlation between NETs and clinical disease activity (DAS28, CDAI, SDAI) was found, but not with laboratory parameters of inflammation including calprotectin. <h3>Conclusion</h3> NETs are elevated in active RA patients but weakly correlated with clinical disease activity. Patients with established RA under biologic or JAKi therapy have low levels of plasma NETs. NETs levels may be influenced by biologic or JAKi treatment. <h3>Reference</h3> [1] Song et al. Frontiers in Immunology 2021 <h3>Acknowledgements:</h3> NIL. <h3>Disclosure of Interests</h3> None Declared.